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The adverse effects of traditional pharmaceutical immunosuppressive regimens have been a major obstacle to successful allograft survival in vascularized composite tissue allotransplantation (VCA) cases. Consequently, there is a pressing need to explore alternative approaches to reduce reliance on conventional immunotherapy. Cell therapy, encompassing immune-cell-based and stem-cell-based regimens, has emerged as a promising avenue of research. Immune cells can be categorized into two main systems: innate immunity and adaptive immunity. Innate immunity comprises tolerogenic dendritic cells, regulatory macrophages, and invariant natural killer T cells, while adaptive immunity includes T regulatory cells and B regulatory cells. Investigations are currently underway to assess the potential of these immune cell populations in inducing immune tolerance. Furthermore, mixed chimerism therapy, involving the transplantation of hematopoietic stem and progenitor cells and mesenchymal stem cells (MSC), shows promise in promoting allograft tolerance. Additionally, extracellular vesicles (EVs) derived from MSCs offer a novel avenue for extending allograft survival. This review provides a comprehensive summary of cutting-edge research on immune cell therapies, mixed chimerism therapies, and MSCs-derived EVs in the context of VCAs. Findings from preclinical and clinical studies demonstrate the tremendous potential of these alternative therapies in optimizing allograft survival in VCAs., Competing Interests: Declaration of competing interest None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Adipose-derived stem cells (ASCs) are recognized for their potential immunomodulatory properties. In the immune system, tolerogenic dendritic cells (DCs), characterized by an immature phenotype, play a crucial role in inducing regulatory T cells (Tregs) and promoting immune tolerance. Notch1 signaling has been identified as a key regulator in the development and function of DCs. However, the precise involvement of Notch1 pathway in ASC-mediated modulation of tolerogenic DCs and its impact on immune modulation remain to be fully elucidated. This study aims to investigate the interplay between ASCs and DCs, focusing the role of Notch1 signaling and downstream pathways in ASC-modulated tolerogenic DCs., Methods: Rat bone marrow-derived myeloid DCs were directly co-cultured with ASCs to generate ASC-treated DCs (ASC-DCs). Notch signaling was inhibited using DAPT, while NFκB pathways were inhibited by NEMO binding domain peptide and si-NIK. Flow cytometry assessed DC phenotypes. Real-time quantitative PCR, Western blotting and immunofluorescence determined the expression of Notch1, Jagged1 and the p52/RelB complex in ASC- DCs., Results: Notch1 and Jagged1 were highly expressed on both DCs and ASCs. ASC-DCs displayed significantly reduced levels of CD80, CD86 and MHC II compared to mature DCs. Inhibiting the Notch pathway with DAPT reversed the dedifferentiation effects. The percentage of induced CD25+/FOXP3+/CD4+ Tregs decreased when ASC-DCs were treated with DAPT (inhibition of the Notch pathway) and si-NIK (inhibition of the non-canonical NFκB pathway)., Conclusions: ASCs induce DC tolerogenicity by inhibiting maturation and promoting downstream Treg generation, involving the Notch and NFκB pathways. ASC-induced tolerogenic DCs can be a potential immunomodulatory tool for clinical application., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary, or financial interest in the products or companies described in this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: The potential of biodegradable magnesium (Mg) skin staple has recently garnered widespread attention due to their biodegradability and biocompatibility rather than traditional stainless steel staples, the most commonly used in current clinical practice. The aim of this study is to evaluate the safety and mechanical properties of a novel biodegradable Mg skin staple., Methods: A prototype of Mg skin staple was designed using a novel ZK60 Mg alloy. The mechanical properties of the staple were evaluated using a universal testing machine. The cytotoxicity of the staple was examined in vitro and the efficacy of the staple in wound closure was assessed in New Zealand rabbits for one and three weeks, respectively., Results: The tensile strength of this Mg alloy is 258.4 MPa with 6.9% elongation. The treatment of HaCaT and L929 cells with the staple extract resulted in over 95% cell viability, indicating no cytotoxicity. In vivo, no tissue irritation was observed. No difference was found in wound healing between the Mg skin staple and the stainless steel staple after one and three weeks in the cutting wound on the back of rabbits. Some Mg skin staples spontaneously dislodged from the skin within three weeks, while others were easily removed., Conclusion: Our results confirm the safety, biocompatibility, and functionality of the novel Mg skin staple in wound closure. The efficacy of the staple in wound closure was demonstrated to be as effectively as conventional staples, with the added benefit of decreased long-term retention of skin staples in the wounds., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to assess the prognostic importance of perinephric fat features in images of patients with non-metastatic renal cell carcinoma (RCC) undergoing surgery., Methods: We enrolled RCC patients who underwent surgical treatment between 2011 and 2019. Two characteristics, including perinephric fat thickness and perinephric fat stranding, were evaluated using preoperative computed tomography or magnetic resonance images. The association between perinephric fat characteristics and disease progression was examined by Kaplan-Meier survival analysis and Cox regression model., Results: In a multivariate Cox proportional hazards model adjusting for tumor stage, intratumoral necrosis, and neutrophil-to-lymphocyte ratio, we found that patients in the thin perinephric fat group (<1 cm) had a poorer progression-free survival (PFS) compared to the thick perinephric fat group (≥1 cm) (HR 2.8; 95% CI 1.175-6.674, p = 0.02). Additionally, the fat stranding group had a poorer PFS than the non-stranding group (HR 3.852; 95% CI 1.082-13.704, p = 0.037). The non-stranding with thick perinephric fat group exhibits the highest cumulative PFS while the stranding with thin perinephric fat group has the lowest cumulative PFS. In receiver operating characteristic curve analysis, combing these two perinephric fat characteristics with tumor stage can achieve a better discriminatory power than tumor stage alone., Conclusions: Our study indicates that the evaluation of image-based perinephric fat features is a simple, straightforward, reproducible tool for predicting RCC prognosis and may assist in preoperative risk stratification., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Introduction: It is critical to preserve adequate vascularization in midface allotransplantation, the major complication of which is inadequate blood supply in palate area supplying mainly by internal maxillary artery. Therefore, the aim of this study is to explore a modified Le Fort II approach entailing midface vascularization enhancement., Materials and Methods: Ten cadaveric heads were used in mock surgery. A conventional approach was used on seven cadaveric heads to harvest external carotid artery-facial artery-internal maxillary artery axis. On the remaining three cadaveric heads, modified Le Fort II approach was applied where the internal maxillary artery was harvested after cutting off zygomatic arches and rami of the mandible., Results: The conventional approach had difficulty harvesting internal maxillary artery, which left the facial artery the only blood supply to midface. Modified Le Fort II approach with Computerized surgical planning (CSP) assisted, on the other hand, could completely unveil and harvest intact internal maxillary artery after osteotomy of mandibular ramus., Conclusion: The modified Le Fort II approach with CSP and ultrasonic bone cutter assisted can maximally preserve internal maxillary system with ease. This approach optimizes midface allotransplantation in clinical practice in future., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Lymphedema is defined as the abnormal accumulation of interstitial fluid in subcutaneous tissues resulting from cancer, cancer treatment (surgery and/or radiotherapy), infection, inflammatory disorders, obesity, and hereditary syndromes. Surgical management of lymphedema can be broadly classified into two categories, reductive surgical techniques such as direct excision, suction assisted protein lipectomy (SAPL) or radical reduction with perforator preservation (RRPP); and physiological surgical procedures such as lymphaticovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT). These techniques and their various combinations were evaluated. The results revealed patients with reversible lymphedema (ISL stage I, mild severity) benefit most from physiological procedures (LVA or VLNT) which can reduce the chance of disease progression to the chronic, solid phase. Reductive techniques such as SAPL, RPPP, or direct excision procedures should be reserved for patients with advanced - severe lymphedema (ISL stages II and especially stage III) as the surgical treatment of choice. In this study, current literature on the surgical treatment of lower extremity lymphedema is reviewed and discussed in conjunction with authors' clinical experiences. An algorithm is presented, based on clinical evidence and experience which aims to provide a structured approach to managing lower limb lymphedema., (Copyright © 2020. Published by Elsevier Taiwan LLC.)

Keloids are considered as benign fibroproliferative skin tumors, and rare cases of malignancies have been reported. We present a case of low-grade myofibroblastic sarcoma arising from a recurrent painful keloid scar on the right chest wall after video-assisted thoracic surgery for pneumothorax in a 77-year-old man. Wide composite excision of the keloid, surrounding ribs, and partial diaphragm were performed. The chest wall pleural defect was reconstructed with Teflon (Chemours, Wilmington, DE), and soft tissue was reconstructed with a transverse rectus abdominis myocutaneous flap. This case highlights that refractory keloids may be considered a harbinger of malignancy., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Follicular thyroid carcinoma (FTC) with sternum metastasis is rarely reported. Conservative treatments always result in a poor prognosis. We report two cases of FTC presenting with a large symptomatic solitary metastatic lesion in the sternum. Surgical intervention included total thyroidectomy, combined with wide composite resection of the sternal manubrium, as well as the adjacent clavicular head and ribs. A large defect with exposed pericardium and great vessels was found post resection in both cases. Because the ipsilateral vessels were sacrificed, a contralateral extended pedicled pectoralis major adipofascial flap was designed and transposed to cover the underlying vital organs. The patients received both adjuvant I-131 and radiotherapy postoperatively. The treatment was uneventful, and the patients are well and asymptomatic 5 years after the treatment. Wide composite resection and appropriate adjuvant therapies may offer a survival benefit in patients with advanced FTC with sternum metastasis., (Copyright © 2012, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.)

Background: After harvesting the fibula flap, pain, sensory disturbance, weakness of donor leg, reduced walking endurance, ankle instability, and lower walking speed had been reported. The aim of this study was to quantitatively assess functional outcome of regular home-based exercise on donor ankle strength, endurance, and walking ability after free fibula flap for mandibular reconstruction., Methods: Fourteen patients were recruited. Objective isokinetic testing and a 6-min walk test (6MWT) were used to evaluate ankle strength/endurance and walking ability, respectively., Results: There was a significant increase in the peak torque of ankle dorsiflexion/foot inversion of the healthy leg and ankle dorsiflexion/foot eversion of the donor leg after exercise (p < 0.05). After home-based exercise, there was reduced asymmetry in the peak torques of ankle dorsiflexion and foot eversion and the total work of foot eversion between the donor and healthy legs. In 6MWT, no significant difference was found between the walking distances before and after exercise., Conclusion: Regular home-based exercise could improve the strength of ankle dorsiflexion and foot eversion of the donor leg, and get more symmetric ankle motor function between the donor and healthy legs.

For buried flaps in the head and neck, direct monitoring of the flap can be extremely difficult. The authors report their experience with 22 patients who underwent pharyngoesophageal reconstruction using an anterolateral thigh (ALT) fasciocutaneous perforator flap with a design that addresses the concerns of buried flap monitoring. This is an observational study of 22 patients, who underwent pharyngoesophageal reconstruction with ALT fasciocutaneous flaps between June 2006 and February 2008. The design of the flap consists of three components: proximal component of flap for pharyngeal reconstruction, mid-component de-epithelized for esophageal-skin flap junction, and distal component either as an external sentinel monitor or for replacing the external neck skin, nourished solely by the suprafascial plexus. The patients' age ranged between 40 and 72 years with a mean age of 55.5 years. The measurements of the skin paddles of the ALT flaps ranged from 10 to 30 cm in length and 6 to 8 cm in width. The flap success rate was 95.5% (21/22). The overall sensitivity and specificity rate of this monitoring method is 100% and 94.7% respectively. There were venous congestions found in four skin paddles. One was demonstrated to be false positive after re-exploration. The other three were true positives and two of these were salvaged successfully. The remaining flap could not be salvaged due to severe deep neck infection. Three patients had a small fistula at the distal end of the esophageal-skin flap junction. All healed spontaneously after conservative treatment. This ALT flap design for pharyngoesophageal defect reconstruction is simple and versatile. The distal skin flap can be utilized as an external sentinel monitor for the buried part of the flap, and for resurfacing of the anterior neck skin if required., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Management of postpneumonectomy empyema has always been a challenging task. Local flaps or free muscle flaps are options for recalcitrant cases when traditional therapeutic attempts fail. This report presents 2 patients with chronic postpneumonectomy empyema who were treated with an anterolateral thigh combined flap consisting of vastus lateralis and rectus femoris muscles. This method showed promising results for reconstruction of large empyema defect., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Reconstruction of a complex knee trauma with knee joint exposure and composite soft tissue and patellar tendon deficiency remains a challenging task. Multiple-stage reconstruction is time-consuming and produces considerable suffering for patients. Early mobilization following knee reconstruction has achieved good outcomes. Herein, we reported one-stage reconstruction with an ALT myocutaneous flap with vascularized fascia lata was utilized for one patient with a large complex knee joint soft tissue defect, and segmental deficiency of the patellar tendon. The fascia lata sheet was rolled to mimic a patellar tendon. The exposed knee joint was obturated by the vastus lateralis muscle of the ALT myocutaneous flap. The skin and soft tissue defect was reconstructed using the skin paddle of the ALT flap. The patient's postoperative course was uneventful. An MRI examination demonstrated good continuity of the reconstructed patellar tendon. The active ROM of the injured knee reached 100 degrees (extension deficiency 20 degrees and flexion 120 degrees ) at 5 years. Objective functional assessment of the patella-femoral joint utilized a kinetic communicator machine (Kin-Com 500H, Chattecx, Chattanooga, TN, USA) revealed still mild extension insufficiency. However, the patient reported that he was able to perform normal daily activities without difficulty at 5-year follow-up.

The biological mechanism underlying steroid therapy for treating keloids remains unclear. Analytical results demonstrated that topical intra-lesional steroid injections suppress vascular endothelial growth factor (VEGF) expression in keloid tissue and induce its regression in vivo. This study investigated whether glucocorticoid (dexamethasone) downregulates VEGF expression and hinders keloid fibroblast (KF) proliferation in keloid regression. Primary KF cultures were treated with various concentrations of dexamethasone, glucocorticoid receptor (GR) antagonist (mifeprostone, RU-486), VEGF-A antibody, VEGF receptor-2 (VEGF-R2) antagonist (SU-5416), and VEGF protein. Analytical results demonstrated that dexamethasone retarded KFs proliferation. However, suppression of fibroblast proliferation by dexamethasone pre-treatment was reduced by adding exogenous VEGF protein. Dexamethasone suppressed endogenous VEGF mRNA induction, protein expressed by KFs, and angiogenesis activity detected by a tube-forming assay of human umbilical vein endothelial cells co-cultured fibroblasts. These effects were reversed by pre-treatment with RU-486, and not by pre-treatment with SU-5416. Thus, dexamethasone induces keloid regression via interaction with the GR and suppresses endogenous VEGF expression and fibroblast proliferation. However, exogenous VEGF promotes fibroblast proliferation through the GR-independent pathway. Modulation of VEGF production may comprise a valuable treatment modality for keloids.

Although previous studies have demonstrated that diabetic nephropathy is attributable to early extracellular matrix accumulation in glomerular mesangial cells, the molecular mechanism by which high glucose induces matrix protein deposition remains not fully elucidated. Rat mesangial cells pretreated with or without inhibitors were cultured in high-glucose or advanced glycation end product (AGE) conditions. Streptozotocin-induced diabetic rats were given superoxide dismutase (SOD)-conjugated propylene glycol to scavenge superoxide. Transforming growth factor (TGF)-beta1, fibronectin expression, Ras, ERK, p38, and c-Jun activation of glomerular mesangial cells or urinary albumin secretion were assessed. Superoxide, not nitric oxide or hydrogen peroxide, mediated high glucose- and AGE-induced TGF-beta1 and fibronectin expression. Pretreatment with diphenyliodonium, not allopurinol or rotenone, reduced high-glucose and AGE augmentation of superoxide synthesis and fibronection expression. High glucose and AGEs rapidly enhanced Ras activation and progressively increased cytosolic ERK and nuclear c-Jun activation. Inhibiting Ras by manumycin A reduced the stimulatory effects of high glucose and AGEs on superoxide and fibronectin expression. SOD or PD98059 pretreatment reduced high-glucose and AGE promotion of ERK and c-Jun activation. Exogenous SOD treatment in diabetic rats significantly attenuated diabetes induction of superoxide, urinary albumin excretion, 8-hydroxy-2'-deoxyguanosine, TGF-beta1, and fibronectin immunoreactivities in renal glomerular mesangial cells. Ras induction of superoxide activated ERK-dependent fibrosis-stimulatory factor and extracellular matrix gene transcription of mesangial cells. Reduction of oxidative stress by scavenging superoxide may provide an alternative strategy for controlling diabetes-induced early renal injury.

Background: Reconstruction of the esophagus for complicated benign stricture or after resection of malignant lesion is still a challenge for surgeons. When abdominal viscera cannot be used, skin flaps are selected for esophageal reconstruction. However, skin flaps for esophageal reconstruction are notorious for leakage, and have not been widely accepted. Prefabrication before microvascular transfer to its final site can improve the result of esophageal reconstruction when skin flaps are used., Methods: Eight patients with complicated corrosive esophagitis had been treated with prefabricated skin flaps for esophageal reconstruction. The procedures are described in detail., Results: All patients healed well without leakage. The barium study showed smooth passage. There was no dysphasia or regurgitation after education. Pulmonary complication happened in only 1 patient. Revision for the distal anastomosis was required in 1 patient due to narrowing. When the skin tube is long, the patients need water (or soup) to facilitate swallowing and occasionally use their hand to help the food passage. This method has the following advantages: (1) healing of the long suture line before transfer to withstand the intestinal juice; (2) reliable viability in the distal part of the flap, especially when an extended length of the flap is required; (3) more length of stable tissue for two-layered, tension-free anastomosis at the junction of skin and gastrointestinal mucosa to prevent leakage; and (4) the flap can be placed in the substernal position to meet the aesthetic requirement of young patients. The disadvantage was the staged operations. However, after prefabrication the transfer becomes safe and free of leakage. The overall morbidity is minimal., Conclusions: In rare situations when skin flaps are used for esophageal reconstruction, prefabrication provides advantages over conventional one-stage methods, although it needs additional procedures. This method is a combination of conventional technique and microsurgery.